治疗脓肿分枝杆菌的双β-内酰胺类药物:证据综述,呼吁对抗生素噩梦采取行动。

IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES
Bianca Maria Longo, Mattia Trunfio, Andrea Calcagno
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引用次数: 0

摘要

脓肿分枝杆菌复合体是一组生长迅速的非结核分枝杆菌(NTM),越来越多地成为机会性病原体。目前针对这些微生物的治疗方案十分有限,而且治疗失败率、毒性和复发率都很高。最近的研究发现,脓肿霉菌细胞壁的合成主要受两类酶(d,d-反肽酶和 l,d-反肽酶)的调控,这两类酶对不同β-内酰胺类药物的抑制作用不同。测试几种 DBL 组合的体外研究显示,在细胞外肉汤培养和细胞内环境中,头孢西丁/亚胺培南、头孢他啶/亚胺培南、头孢唑肟/头孢他啶和头孢唑肟/亚胺培南具有协同作用。添加针对脓肿病菌β-内酰胺酶的特异性β-内酰胺酶抑制剂(BLIs)并不能显著提高DBL组合的活性。但缺乏体内数据。我们回顾了基于DBL/DBL-BLI疗法治疗脓肿病菌感染的文献,以提高人们对这一前景广阔但却被忽视的治疗方案的关注,并为未来的临床前和临床研究提供指导。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dual β-lactams for the treatment of Mycobacterium abscessus: a review of the evidence and a call to act against an antibiotic nightmare.

Mycobacterium abscessus complex is a group of rapidly growing non-tuberculous mycobacteria (NTM), increasingly emerging as opportunistic pathogens. Current treatment options for these microorganisms are limited and associated with a high rate of treatment failure, toxicity and recurrence. In search of new therapeutic strategies, interest has grown in dual β-lactam (DBL) therapy, as research recently discovered that M. abscessus cell wall synthesis is mainly regulated by two types of enzymes (d,d-transpeptidases and l,d-transpeptidases) differently susceptible to inhibition by distinct β-lactams. In vitro studies testing several DBL combinations have shown synergy in extracellular broth cultures as well as in the intracellular setting: cefoxitin/imipenem, ceftaroline/imipenem, ceftazidime/ceftaroline and ceftazidime/imipenem. The addition of specific β-lactamase inhibitors (BLIs) targeting M. abscessus β-lactamase did not significantly enhance the activity of DBL combinations. However, in vivo data are lacking. We reviewed the literature on DBL/DBL-BLI-based therapies for M. abscessus infections to raise greater attention on this promising yet overlooked treatment option and to guide future preclinical and clinical studies.

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来源期刊
CiteScore
9.20
自引率
5.80%
发文量
423
审稿时长
2-4 weeks
期刊介绍: The Journal publishes articles that further knowledge and advance the science and application of antimicrobial chemotherapy with antibiotics and antifungal, antiviral and antiprotozoal agents. The Journal publishes primarily in human medicine, and articles in veterinary medicine likely to have an impact on global health.
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